The Treasury Department move freezes any US assets held by 29 members of the regime's upper echelon -- including the ministers of finance, economy and justice, and the central bank governor -- and bans US business ties with them.

While the US had already introduced sanctions against around 100 people or entities linked to the regime, the move represented a significant stepping up of pressure on Assad's inner circle.

Until now those not directly involved in the violence have largely dodged sanctions, as Washington tried to cleave divisions within the regime and encourage defections.

Among the other ministers included in Wednesday's actions were those responsible for agriculture, housing, health, education, environment, culture and oil.

Many were appointed less than a month ago when Assad announced a new cabinet in the wake of controversial parliamentary elections that were boycotted by the opposition.

US officials denied that the timing of the sanctions was linked to a bombing earlier Wednesday that killed Defense Minister General Daoud Rajha, Assad's brother-in-law Assef Shawkat and General Hassan Turkmani, the head of the regime's crisis cell.

But it appears President Barack Obama's administration is treating the blast as a potential turning point in the 16-month-old uprising.

"It's clear that the Assad regime is losing control of Syria," National Security Council spokesman Tommy Vietor said, echoing Defense Secretary Leon Panetta, who said earlier that Syria was "spinning out of control."

Panetta called for "maximum pressure on Assad to do what's right, to step down and to allow for that peaceful transition."

Syrian opposition forces have recently appeared emboldened, launching four straight days of attacks in Damascus and claiming responsibility for Wednesday's devastating attack.

According to the Syrian Observatory for Human Rights 16 people were killed in violence in Damascus on Wednesday, bringing the nationwide total for the day to nearly 100.

"The United States does not welcome further bloodshed in Syria," said State Department spokesman Patrick Ventrell.

"We know however that these men were key architects of the Assad's regime assault on the Syrian people."

Amid the violence, the White House stressed the need for a political transition to avoid a "lengthy and bloody sectarian civil war."

Obama spoke on the phone with his Russian counterpart Vladimir Putin about the crisis Wednesday in a bid to bridge differences over Assad's fate and the type of political transition that should follow him.

The White House said no deal was found but the pair "agreed on the need to support a political transition as soon as possible that achieves our shared goal of ending the violence and avoiding a further deterioration of the situation."

Meanwhile at the United Nations in New York, the US continued to press for a Security Council resolution that would allow broader international sanctions against the regime.

In the face of Russian and Chinese opposition, the vote was pushed back until Thursday.

"We will be voting tomorrow morning," said Britain's UN Ambassador Mark Lyall Grant, whose country took the lead in drawing up the sanctions resolution.

Russia has threatened to veto any resolution that gives the Security Council the power to take military actions should sanctions fail.

The mandate of the UN Supervision Mission in Syria, or UNSMIS, ends on Friday and without a resolution, the UN may have to hurriedly withdraw the nearly 300 unarmed observers now in Damascus.

More than 17,000 people have been killed since a popular uprising against Assad began in March 2011, activists say.